Covid19Phase 2/3PHRUCov01NCT04581915
PHRU CoV01 A Trial of Triazavirin (TZV) for the Treatment of Mild-moderate COVID-19
A Phase 2/3 study testing Triazavirin (Riamilovir) in people with Covid19, run by Wits Health Consortium (Pty) Ltd at 1 site in South Africa.
Trial summary
A) Phase II: Early viral responses to triazavirin In hospitalised patients with mild-moderate COVID-19, in addition to standard of care therapy, treatment with triazavirin 250mg three times daily for five days, the slope of increase of the Ct values of serial nasopharyngeal swabs to 12 days after initiation of… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Covid19
- What is being tested?
- Triazavirin (Riamilovir)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 74 participants
- Where
- 1 siteSouth Africa
- Study dates
- 8 Sep 2020to 20 Apr 2021
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients ≥18 years of age, who have a clinical presentation suggestive of COVID-19, or who have had a molecular laboratory assay that confirms SARS-CoV-2 infection that was collected prior to the first dose of study treatment.
- Patients with mild to moderate COVID-19 who need admission and may require oxygen at admission but not yet requiring escalation of oxygen therapy to CPAP, high flow nasal oxygen or intubation. We will not include patients with laboratory confirmation of SARS-CoV-2 who report no symptoms at all.
- Able to provide own consent
- Willing to have HIV test - unless already has clinical documentation of HIV infection (as evidenced by a HIV rapid test result during the admission, or any one of the following: a positive HIV ELISA assay; an ART prescription; a pill container for ART with the patient's name; a hard copy or an electronic viral load result that includes the patient's name showing detectable HIV copies; clinical documentation of HIV sero-positivity included in the medical record)
- Randomisation must occur within 48 hours of first COVID-19 diagnosis during the current illness.
Who cannot join
- Women who are pregnant or breastfeeding at the time of enrolment
- Weight <40kg.
- Evidence of current liver disease (AST/ALT >3x ULN ; total bilirubin>3xULN or prior history of cirrhosis or other chronic liver disease)
- Renal dysfunction as evidenced by an estimated glomerular filtration rate (eGFR) <60ml/min, or prior/current diagnosis of chronic kidney disease.
- Prior receipt of any treatment with putative or proven anti-SARS-Cov-2 activity apart from the following: chloroquine, hydroxychloroquine, or ritonavir/lopinavir initiated no more than 12 hours prior to first receipt of TZV/placebo for this trial. Antiretrovirals initiated prior to admission as treatment for HIV, supportive, steroidal and non-steroidal anti-inflammatory, or anti-pyretic treatments are allowed.
- Indication for immediate initiation of antiretroviral therapy in HIV-infected patients, who are unable to delay ART initiation or re-initiation until the treatment phase of this study is complete.
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- Permanently lives or works more than 120km from the hospital where recruited
- Unable to provide own consent
- In the opinion of either the attending doctor, or a study investigator that the patient is not a candidate for a clinical trial
- Receipt of anti-epileptic medication, warfarin or TB treatment at the time of recruitment or during the receipt of trial treatment.
- Enrolled currently in a trial of novel preventive treatment or treatment of SARS-CoV-2.
- Potential participants who are investigational site staff members, or relatives of a site staff member, or those who are employees of PharmaCentrix involved in the conduct of the trial.
- -
Trial locations and contacts
1 site in 1 country.
South Africa1 site
The Perinatal HIV Research Unit - Matlosana
Klerksdorp, North West
About this study
Official title: A Pragmatic, Individually Randomised, Double-blind, Placebo-controlled Trial of Triazavirin (TZV) for the Treatment of Mild-moderate SARS-CoV-2 Infection A Phase II and III Clinical Trial
- Phase II: Early viral responses to triazavirin In hospitalised patients with mild-moderate COVID-19, in addition to standard of care therapy, treatment with triazavirin 250mg three times daily for five days, the slope of increase of the Ct values of serial nasopharyngeal swabs to 12 days after initiation of treatment will be ≥24% higher than in hospitalised patients receiving standard of care treatment only.
- Phase III: Efficacy of triazavirin to improve clinical outcomes In hospitalised patients with mild-moderate laboratory proven COVID-19, in addition to standard of care therapy, treatment with triazavirin 250mg three times daily for five days will reduce a composite outcome - death; ICU admission or mechanical ventilation; or prolonged duration of admission- by ≥29% when compared to the composite outcome in hospitalised patients receiving standard of care therapy only.
Read the detailed description
Design: This will be a two-site, iterative, double-blinded, randomized, placebo controlled, 2-arm, phase II and III superiority trial. Participants will be randomised 1:1 to each arm. The first part of the trial will recruit 64 evaluable patients to validate a biological effect of triazavirin on SARS-CoV-2. If triazavirin indeed has a demonstrable effect, the trial will continue to randomise another 316 evaluable participants to ascertain if there is a clinical benefit.
Participants: Three hundred and eighty evaluable patients with newly diagnosed, laboratory confirmed, mild-moderate (including asymptomatic) SARS-CoV-2 infection. Men and women will be recruited in a ratio of 3:2.
Study sites: Tshepong Provincial Hospitals in NW Province. Field Hospitals in Gauteng (NASREC) and North West (West Vaal) will be included if possible.
Study Duration: Follow up will be approximately 32 days; the total duration of from recruitment of first patients to last follow follow up visit is 15 months.
Population: Adult in-patients, ≥18 years and older, with a recent diagnostic test positive for SARS-CoV-2. Men and women will be recruited, in a ratio of 3:2.
Intervention: After verbal informed consent is provided, participants will be randomly assigned to receive either five days of triazavirin 250mg p.o three times daily, or placebo at the same dosing schedule, in addition to standard of care therapy prescribed by the attending physicians.
Primary Objectives:
To ascertain whether a 5-day course of TZV (250mg taken orally three times per day) in addition to standard of care treatment for in-patients with mild-moderate disease caused by SARS-Cov-2 is effective in:
- Enhancing the rate of viral clearance from the nasopharynx compared to placebo.
- To demonstrate a favourable outcome in the intervention arm compared to placebo arm using a composite clinical outcome that consists of the earliest occurrence of any of the following:
- Death
- Admission to ICU or mechanical ventilation required (continuous positive airway pressure, high flow nasal oxygen or intubation);
- Prolonged duration of admission lasting >14 days (this includes patients who are discharged and re-admitted within 48 hours of leaving the hospital).
- To ascertain safety and tolerability of the investigational drug TZV
Secondary objectives:
- To compare time to the first of two consecutive nasopharyngeal swabs that are negative for SARS-CoV-2 between the arms.
- To compare the proportion of participants whose nasopharyngeal swabs are negative for SARS-CoV-2 two days after the end of study treatment.
- To compare symptom reduction and improvement in clinical measures between arms
- To compare efficacy of nasopharyngeal swabs with salivary specimens in assessing viral responses to treatment.
- Conditions
- Covid19
- Being tested
- Triazavirin (Riamilovir), Placebo
- Keywords
- SARS CoV2, Triazavirin, Novel anti-viral agent
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Triazavirin (Riamilovir)Drug
Capsule - 250mg 8 hourly po
PlaceboOther
Placebo capsule
| Study group | Role | What they receive |
|---|---|---|
| Interventional | Experimental | Participants to receive Triazavirin 250mg po 8 hourly for 5 days Receives: Drug: Triazavirin (Riamilovir) |
| Control | Placebo comparator | Participants to receive placebo po 8 hourly for 5 days Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
To compare the slope of cycle threshold(Ct) values of nasopharyngeal swabs in people receiving Triazavirin versus placebo
To ascertain that indeed there is a biological effect of Triazavirin, we will compare slope of cycle threshold (Ct) values of nasopharyngeal swabs taken from all patients in the Phase II part of the trial. We require at least a 24% difference in slope.
Measured: 11 days per patient
To assess the proportion of patients who progress to severe COVID-19 and the proportion who need ICU or die.
We have selected a composite measure including three adverse outcomes, all of which have serious implications for the patient and the health system. We will combine: deaths; ICU admissions or mechanical ventilation; and prolonged hospital stays -defined in this study as >14 days.
Measured: 1 month per patient
To determine the proportion of patients who develop grade 3 or grade 4 adverse events on treatment
We will compare rates of grade 3 and worse adverse events that occur whilst on treatment, and for up to 30 days after randomisation. We will also report on tolerability, by comparing the proportions by arm of those who had placebo/Triazavirin withheld permanently.
Measured: 1 month per patient
To determine the proportion of patients who stop taking either placebo/Triazavirin
We will report on tolerability by comparing the proportions by arm who had placebo/Triazavirin withheld permanently.
Measured: 1 month per patient
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2020
- Study start8 Sep 2020
- Primary completion20 Apr 2021
- Study completion20 Apr 2021
Why it stopped: DSMB report
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Covid19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants are assigned to an interventional group or a placebo group after randomisation in parallel for the duration of the study.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 74 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wits Health Consortium (Pty) Ltd
- Sponsor type
- University, hospital or other
- Collaborators
- PharmaCentrix (Pty) Ltd, Perinatal HIV Research Unit of the University of the Witswatersrand
- Responsible party
- Sponsor
- Investigators
- Neil A Martinson, MBChB, Principal investigator, Perinatl HIV Research Unit CEO
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04581915
- Sponsor's protocol ID
- PHRU CoV01
- Acronym
- PHRUCov01
- Status last verified
- Oct 2020
- First submitted
- 16 Sep 2020
- Last updated
- 2 Aug 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pragmatic, Individually Randomised, Double-blind, Placebo-controlled Trial of Triazavirin (TZV) for the Treatment of Mild-moderate SARS-CoV-2 Infection A Phase II and III Clinical Trial
- ClinicalTrials.gov ID
- NCT04581915
- Acronym / sponsor ID
- PHRUCov01 / PHRU CoV01
- Conditions
- Covid19
- Keywords
- SARS CoV2, Triazavirin, Novel anti-viral agent
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: DSMB report
- Enrolment
- 74 participants (actual)
- Lead sponsor
- Wits Health Consortium (Pty) LtdUniversity, hospital or other
- Collaborators
- PharmaCentrix (Pty) Ltd, Perinatal HIV Research Unit of the University of the Witswatersrand
- Study start
- 8 Sep 2020 (actual)
- Primary completion
- 20 Apr 2021 (actual)
- Study completion
- 20 Apr 2021 (actual)
- First posted
- 9 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
- Phase II: Early viral responses to triazavirin In hospitalised patients with mild-moderate COVID-19, in addition to standard of care therapy, treatment with triazavirin 250mg three times daily for five days, the slope of increase of the Ct values of serial nasopharyngeal swabs to 12 days after initiation of treatment will be ≥24% higher than in hospitalised patients receiving standard of care treatment only.
- Phase III: Efficacy of triazavirin to improve clinical outcomes In hospitalised patients with mild-moderate laboratory proven COVID-19, in addition to standard of care therapy, treatment with triazavirin 250mg three times daily for five days will reduce a composite outcome - death; ICU admission or mechanical ventilation; or prolonged duration of admission- by ≥29% when compared to the composite outcome in hospitalised patients receiving standard of care therapy only.
Detailed description
Design: This will be a two-site, iterative, double-blinded, randomized, placebo controlled, 2-arm, phase II and III superiority trial. Participants will be randomised 1:1 to each arm. The first part of the trial will recruit 64 evaluable patients to validate a biological effect of triazavirin on SARS-CoV-2. If triazavirin indeed has a demonstrable effect, the trial will continue to randomise another 316 evaluable participants to ascertain if there is a clinical benefit.
Participants: Three hundred and eighty evaluable patients with newly diagnosed, laboratory confirmed, mild-moderate (including asymptomatic) SARS-CoV-2 infection. Men and women will be recruited in a ratio of 3:2.
Study sites: Tshepong Provincial Hospitals in NW Province. Field Hospitals in Gauteng (NASREC) and North West (West Vaal) will be included if possible.
Study Duration: Follow up will be approximately 32 days; the total duration of from recruitment of first patients to last follow follow up visit is 15 months.
Population: Adult in-patients, ≥18 years and older, with a recent diagnostic test positive for SARS-CoV-2. Men and women will be recruited, in a ratio of 3:2.
Intervention: After verbal informed consent is provided, participants will be randomly assigned to receive either five days of triazavirin 250mg p.o three times daily, or placebo at the same dosing schedule, in addition to standard of care therapy prescribed by the attending physicians.
Primary Objectives:
To ascertain whether a 5-day course of TZV (250mg taken orally three times per day) in addition to standard of care treatment for in-patients with mild-moderate disease caused by SARS-Cov-2 is effective in:
- Enhancing the rate of viral clearance from the nasopharynx compared to placebo.
- To demonstrate a favourable outcome in the intervention arm compared to placebo arm using a composite clinical outcome that consists of the earliest occurrence of any of the following:
- Death
- Admission to ICU or mechanical ventilation required (continuous positive airway pressure, high flow nasal oxygen or intubation);
- Prolonged duration of admission lasting >14 days (this includes patients who are discharged and re-admitted within 48 hours of leaving the hospital).
- To ascertain safety and tolerability of the investigational drug TZV
Secondary objectives:
- To compare time to the first of two consecutive nasopharyngeal swabs that are negative for SARS-CoV-2 between the arms.
- To compare the proportion of participants whose nasopharyngeal swabs are negative for SARS-CoV-2 two days after the end of study treatment.
- To compare symptom reduction and improvement in clinical measures between arms
- To compare efficacy of nasopharyngeal swabs with salivary specimens in assessing viral responses to treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Participants are assigned to an interventional group or a placebo group after randomisation in parallel for the duration of the study.
| Arm | Type | Receives |
|---|---|---|
| Interventional | Experimental | Drug: Triazavirin (Riamilovir)Participants to receive Triazavirin 250mg po 8 hourly for 5 days |
| Control | Placebo comparator | Other: PlaceboParticipants to receive placebo po 8 hourly for 5 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patients ≥18 years of age, who have a clinical presentation suggestive of COVID-19, or who have had a molecular laboratory assay that confirms SARS-CoV-2 infection that was collected prior to the first dose of study treatment.
- Patients with mild to moderate COVID-19 who need admission and may require oxygen at admission but not yet requiring escalation of oxygen therapy to CPAP, high flow nasal oxygen or intubation. We will not include patients with laboratory confirmation of SARS-CoV-2 who report no symptoms at all.
- Able to provide own consent
- Willing to have HIV test - unless already has clinical documentation of HIV infection (as evidenced by a HIV rapid test result during the admission, or any one of the following: a positive HIV ELISA assay; an ART prescription; a pill container for ART with the patient's name; a hard copy or an electronic viral load result that includes the patient's name showing detectable HIV copies; clinical documentation of HIV sero-positivity included in the medical record)
- Randomisation must occur within 48 hours of first COVID-19 diagnosis during the current illness.
Key exclusion criteria (13 listed)
- Women who are pregnant or breastfeeding at the time of enrolment
- Weight <40kg.
- Evidence of current liver disease (AST/ALT >3x ULN ; total bilirubin>3xULN or prior history of cirrhosis or other chronic liver disease)
- Renal dysfunction as evidenced by an estimated glomerular filtration rate (eGFR) <60ml/min, or prior/current diagnosis of chronic kidney disease.
- Prior receipt of any treatment with putative or proven anti-SARS-Cov-2 activity apart from the following: chloroquine, hydroxychloroquine, or ritonavir/lopinavir initiated no more than 12 hours prior to first receipt of TZV/placebo for this trial. Antiretrovirals initiated prior to admission as treatment for HIV, supportive, steroidal and non-steroidal anti-inflammatory, or anti-pyretic treatments are allowed.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Triazavirin (Riamilovir)Capsule - 250mg 8 hourly po | Drug | Interventional |
| PlaceboPlacebo capsule | Other | Control |
Primary outcome
To compare the slope of cycle threshold(Ct) values of nasopharyngeal swabs in people receiving Triazavirin versus placebo
Time frame: 11 days per patient
To ascertain that indeed there is a biological effect of Triazavirin, we will compare slope of cycle threshold (Ct) values of nasopharyngeal swabs taken from all patients in the Phase II part of the trial. We require at least a 24% difference in slope.
To assess the proportion of patients who progress to severe COVID-19 and the proportion who need ICU or die.
Time frame: 1 month per patient
We have selected a composite measure including three adverse outcomes, all of which have serious implications for the patient and the health system. We will combine: deaths; ICU admissions or mechanical ventilation; and prolonged hospital stays -defined in this study as >14 days.
To determine the proportion of patients who develop grade 3 or grade 4 adverse events on treatment
Time frame: 1 month per patient
We will compare rates of grade 3 and worse adverse events that occur whilst on treatment, and for up to 30 days after randomisation. We will also report on tolerability, by comparing the proportions by arm of those who had placebo/Triazavirin withheld permanently.
To determine the proportion of patients who stop taking either placebo/Triazavirin
Time frame: 1 month per patient
We will report on tolerability by comparing the proportions by arm who had placebo/Triazavirin withheld permanently.
Results and safety
The study was stopped early (reason given: DSMB report). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Aug 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Neil A Martinson, MBChB principal investigator
Perinatl HIV Research Unit CEO
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Triazavirin (Riamilovir) in people with Covid19, run by Wits Health Consortium (Pty) Ltd at 1 site in South Africa.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 2 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: DSMB report). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To compare the slope of cycle threshold(Ct) values of nasopharyngeal swabs in people receiving Triazavirin versus placebo (time frame: 11 days per patient). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Aug 2022.